RCTs are considered the gold standard for demonstrating the efficacy of medicinal products and for obtaining an initial estimate of the risk of adverse outcomes. However, as is well understood, these data are often not necessarily indicative of the benefits, risks or comparative effectiveness of an intervention when used in clinical practice populations. The IMI GetReal Glossary defines a pragmatic clinical trial (PCT) as ‘a study comparing several health interventions among a randomised, diverse population representing clinical practice, and measuring a broad range of health outcomes.’ PCTs are focused on evaluating benefits and risks of treatments in patient populations and settings more representative of routine clinical practice. To ensure generalisability, pragmatic trials should represent the patients to whom the treatment will be applied, for instance, inclusion criteria would be broad (e.g. allowing co-morbidity, co-medication, wider age range), the follow-up would be minimized and allow for treatment switching etc. Monitoring safety in a phase III real-world effectiveness trial: use of novel methodology in the Salford Lung Study (Pharmacoepidemiol Drug Saf. 2017;26(3):344-352) describes the model of a phase III pragmatic RCT where patients were enrolled through primary care practices using minimal exclusion criteria and without extensive diagnostic testing and where potential safety events were captured through patients’ electronic health records and in turn triggered review by the specialist safety team.
Pragmatic explanatory continuum summary (PRECIS): a tool to help trial designers (CMAJ 2009; 180: E45-57) is a tool to support pragmatic trial designs and helps define and evaluate the degree of pragmatism. The PRECIS tool has been further refined and now comprises nine domains each scored on a 5 point Likert scale ranging from very explanatory to very pragmatic with an exclusive focus on the issue of applicability (The PRECIS-2 tool: designing trials that are fit for purpose. BMJ 2015; 350: h2147). A checklist and additional guidance is also provided in Improving the reporting of pragmatic trials: an extension of the CONSORT statement (BMJ 2008; 337 (a2390): 1-8).
|10. Specific topics|
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|